Medical aerosol non-diluting holding chamber

ABSTRACT

A medical aerosol delivery device comprises a housing having a first opening and a second opening and defining a fluid passage between the first and second openings. The housing comprising a pressurized medical aerosol canister actuator having a canister receptacle disposed within the fluid passage and having a valve chamber comprising a fine bore nozzle positioned to direct atomized medicament toward the first opening. The fluid passage includes an annular portion bypassing the canister receptacle and the housing comprises a movable closure member for selectively obstructing the fluid passage.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.12/790,652 filed on May 28, 2010, now U.S. Pat. No. 8,251,063 which is acontinuation of U.S. patent application Ser. No. 11/209,391 filed onAug. 24, 2005, now U.S. Pat. No. 7,726,310.

TECHNICAL FIELD

The present disclosure relates to medical aerosol delivery devices.

BACKGROUND

Recent analysis of the public health risks and benefits of replacingcigarettes with a deep nicotine aerosol inhaler (if one were to exist)suggests that such a replacement would have a favourable impact (SumnerII W “Estimating the health consequences of replacing cigarettes withnicotine inhalers” Tobacco Control 2003; 12:124-132). The difficultiesarise in developing a device that generates a sufficiently fine aerosolto allow peripheral lung delivery like that of a cigarette in a costeffective and operationally acceptable manner to current smokers,whether or not they intent to quit using nicotine. With currentlyavailable nicotine replacement therapy (gum, patch, nasal inhaler, oralvapour inhaler) most attempts at smoking cessation fail, and relapserates remain over 75%. Many hard core smokers suffer from an underlyingpsychiatric problem that nicotine may help to ameliorate (Pomerleau CS“Co-factors for smoking and evolutionary psychobiology”, Addiction 1997;92:397-408). None of the available nicotine delivery devices listedabove mimic a cigarette in terms of the rapid puff-by-puff delivery ofan arterial bolus that reaches the brain within seconds, and this mayexplain why most individuals relapse to cigarette smoking While smoking,peak arterial plasma nicotine concentration may be 10 times greater thanvenous concentrations. It is only by absorption through the lungs thatthe rapid arterial bolus nicotine delivery of a cigarette can beachieved, as opposed to the relatively slower venous delivery via buccalor nasal mucosa or skin, which is characteristic of current nicotinedelivery devices including the oral vapour inhaler. The key to efficientarterial (central nervous system) nicotine delivery is the particle sizeof the nicotine aerosol. Nicotine vapour entering the mouth condensesonto the mucosal surface of the mouth and throat. Large aerosol dropletsaffect the upper airway as well. Only nicotine carried by fine dropletsor particles is available for absorption into the pulmonary circulationand reaches the brain quickly in high concentration. Cigarette smokeparticles have a mass median aerodynamic diameter (MMAD) of 0.4 μm. Suchsmall particles deposit mainly in the alveoli of the lung from whichthey may be rapidly absorbed into the pulmonary circulation.

Recent improvements in the technology of medicinal inhalers for asthmaand chronic lung disease has led to the development of solutionformulations for pressurised metered-dose inhalers (pMDIs) that cangenerate fine droplet aerosols, improving upon that of pMDIs using solidparticle suspension formulations and dry powder inhaler technology whichare inherently limited in their potential to go into the ultra-fineparticle size range. Preliminary tests of ahydrofluoroalkane/ethanol/nicotine solution formulation pMDI has shownan MMAD of 1.5 μm (Andrus P G et. al. “Nicotine microaerosol inhaler”1999 Canadian Respiratory Journal; Vol. 6 No 6:509-512), which issufficiently small to allow cigarette simulating peripheral lungdelivery. The hydrofluoroalkane/ethanol solution has also been developedto replace the marijuana cigarette (Davies, R. J. et al. U.S. PatentApplication 20050061314 A1, Mar. 24, 2005; and Peart, J. et al. U.S.Patent Application 20040258622 A1, Dec. 23, 2004) for the same reasonsas those which apply to nicotine, and in recognition of the manymedicinal benefits of cannabinoids (i.e. tetrahydrocannabinol (THC)) intreating chronic pain and nausea. That is, nicotine and cannabis havebeen historically and are presently used most efficiently andeffectively by deep inhalation, and HFA solution formulations allow thesimulation of this where other inhaler technologies fall short.

The parameters of smoking (number of puffs per cigarette, number ofcigarettes per day) are not random, but have been refined by userbehaviour and preference over the long history of cigarette smoking fortherapeutic effect. A further difficulty, however, in the simulation ofsmoking by inhaler is the number of puffs that are typically inhaled inthe course of a day. As a result of the high efficiency of pulmonarycirculation delivery by a deep inhaler or a cigarette, a unit dose ofone cigarette equivalent is best delivered by several puffs over severalminutes. If the entire unit dose were delivered in one puff by deepinhalation, this would be less enjoyable and potentially dangerouslyover stimulating to the user. The entire dose could be delivered to theupper airway in one puff, for example the buccal or nasal mucosa,because it would effectively be delivered more slowly as it is moregradually absorbed into the venous circulation. This of course forgoesthe advantages and user preferences for deep inhalation as describedabove. pMDIs for asthma or emphysema are intended to be discharged 4 to8 times per day giving the inhaler's 200 puffs a life of about a month.Typically a smoker inhales 10 times per cigarette for 20 cigarettes perday thereby using up one inhaler equivalent per day. This rate ofinhaler expenditure is undesirable from both a cost and useracceptability standpoint.

SUMMARY

A holding chamber is used to hold a multiple-inhalation concentratedaerosol cloud which can be drawn upon several times from a singleactuation of the inhaler. Holding chambers are well known and used toimprove efficiency of medicinal aerosol delivery. Typically they haveone way valves near the mouthpiece to allow multiple inhalations of thechamber's contents so that the dose is fully received. With eachinhalation however, ambient air is drawn into the chamber and mixesfreely with the remaining contents. Therefore the concentration of themedicinal aerosol drops off exponentially with successive inhalations.To satisfactorily simulate the cigarette, each inhalation shouldpredictably be of the same concentration. With the present device, theuser may draw upon a fraction of the holding chamber's contents at atime, and then deeply inhale ambient air to send the dose to the lungs.With each inhalation the chamber further collapses so that theconcentration of the aerosol within the chamber remains constant. Inthis manner, a single actuation of a concentrated aerosol from theinhaler provides several equal inhalations, thereby greatly extendingthe life of the inhaler. The gradual emptying of the bag is analogous tothe burning down of the cigarette. The user need not coordinate inhaleractuation with inhalation, and need not keep track of number ofinhalations to get a unit dose (cigarette equivalent) as the empty bagindicates and regulates the unit dose.

In one embodiment, a pressurised metered-dose inhaler canister containsa solution formulation of nicotine or a cannabinoid in HFA propellantsuch that a fine microaerosol may be generated. The canister is housedwithin a standard L-shaped cylindrical actuator. A flexible bag aerosolholding chamber bag is sealed around the outlet passage of the actuatorto receive the microaerosol upon actuation of the canister. Anelastic-loaded mouthpiece is sealed around the inlet passage of theactuator so that the user may break the seal around the inlet passage bywithdrawing the mouthpiece, thus allowing inhalation of a portion of theaerosol contents of the chamber. The inlet passage automatically resealsunder the elastic tension as the mouthpiece is released by the user. Theuser subsequently draws upon the chamber's contents a number of times ata frequency analogous to smoking a cigarette until the chamber is fullycollapsed, such that one inhaler actuation and one filled holdingchamber are comparable to one cigarette. The holding chamber is foldedand stowed within the actuator's outlet passage when not in use.

In one embodiment, a medical aerosol delivery device comprises a housinghaving a first opening and a second opening and defining a fluid passagebetween the first and second openings. The housing comprises apressurized medical aerosol canister actuator having a canisterreceptacle disposed within the fluid passage and having a valve chambercomprising a fine bore nozzle positioned to direct atomized medicamenttoward the first opening. The fluid passage includes an annular portionbypassing the canister receptacle, and the housing comprises a movableclosure member for selectively obstructing the fluid passage.

The closure member may cooperate with the actuator for releasing ametered dose of medicament.

A collapsible holding chamber may be sealingly secured to the firstopening for sealing the first opening, with the first openingcommunicating with an interior volume of the holding chamber.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a profile of the inhaler after inflation of the flexibleholding chamber and actuation of the canister;

FIG. 2 is a profile of the inhaler during an inhalation by the user; and

FIG. 3 is profile of the inhaler while not in use showing stowage of theflexible holding chamber.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

A pressurised medical aerosol canister 10 with valve 11 contains asolution formulation 12 of nicotine or a cannabinoid (i.e. THC) inhydrofluoroalkane propellant. Ethanol may also be present as aco-solvent. The canister 10 is placed in an L-shaped actuator 13 withvalve chamber 14. The stem of the valve 11 sits in the valve chamber 14,such that when the valve is actuated by pressure applied to the base 15of the canister 10, a single metered dose of the nicotine or cannabinoidsolution formulation 12 is sent through a fine bore nozzle 16 in thevalve chamber 14 causing a fine microaerosol cloud 17 to leave theactuator 13 via its outlet passage 18, to be held in a flexible aerosolholding chamber 19 which is air-tightly sealed in a fixed manner aroundthe outlet orifice 18. The inlet passage 20 of the actuator 13 isair-tightly sealed in a sliding manner by an actuator cap 21 with flange22 and baseplate 23. The flange 22 is made of semi-rigid rubber orplastic so that it may slide along the outside of the actuator 13 duringactuation of the canister 10. The base plate 23 is held flatly againstthe base 15 of the canister 10 by an elastic cord 24 which joins theactuator cap 21 to the actuator 13. A mouthpiece 25 is connected to thecap baseplate 23 via a hole 26 in the center of the baseplate 23. Thefollowing is the method by which the device is used in the simulation ofthe smoking of a cigarette: Before use, the holding chamber 19 is foldedin its stowed position within the outlet passage 18 of the actuator 13.Using the mouthpiece 25, the baseplate 23 is lifted from its seal withcanister base 15, such that the user may inflate the holding chamber 19by blowing air through the mouthpiece 25, into the actuator 13 aroundthe canister 10 and then into the holding chamber 19. The mouthpiece isthen released and the baseplate 23 is returned to its sealed positionagainst the canister base 15. The baseplate 23 is then pressed towardsthe actuator 13 in the usual manner by which pMDIs are actuated so thata single metered dose leaves the canister 10 through the valve stem 11,into the valve chamber 14, through the nozzle 16, out through theactuator outlet passage 18, and into the pre-inflated holding chamber19. At this point the nicotine or cannabinoid microaerosol cloud 17 isair-tightly held within the holding chamber and adjoining actuator asseen in FIG. 1. The first inhalation may then be taken by the user byusing the mouthpiece 25 to again lift the baseplate 23 from its sealwith the canister base 15 allowing passage by inhalation of a portion ofthe aerosol cloud 17 into the user's mouth. The mouthpiece 25 is thenreleased again resealing the actuator 13 and chamber 19. The user maythen take a deeper inhalation of ambient air thereby washing thenicotine or THC microaerosol deep into the lungs in the same manner asis usually done during cigarette smoking. At this point the chamber canbe put down analogous to the placing of a cigarette in an ashtray as theelastic 24 maintains the air-tight seal even if a small amount ofpressure is applied to the outside of the chamber 19. The user thentakes 5-10 repeat inhalations from the chamber 19, until the aerosolcloud 17 is depleted and the chamber 19 fully collapsed, thus completinga cycle equivalent to smoking a single cigarette. The chamber 19 isagain stuffed into the outlet passage 18 so that the device occupiesonly the volume of the actuator 13 for convenient pocket or pursecarrying. The chamber 19 is comprised of a thin plastic bag that can besealed around the outlet passage 18 by a circumferential elastic bandaround the actuator 13 at its outlet end. The bag can therefore bereplaced frequently for hygienic reasons.

What is claimed is:
 1. A medical aerosol delivery device, comprising: ahousing having a first opening and a second opening and defining a fluidpassage between the first and second openings; the housing comprising apressurized medical aerosol canister actuator having a canisterreceptacle disposed within the fluid passage and having a valve chambercomprising a fine bore nozzle positioned to direct atomized medicamenttoward the first opening; the fluid passage including an annular portionbypassing the canister receptacle; the housing comprising a movableclosure member for selectively obstructing the fluid passage.
 2. Themedical aerosol delivery device of claim 1, wherein the closure membercooperates with the actuator for releasing a metered dose of medicament.3. The medical aerosol delivery device of claim 2, further comprising: acollapsible holding chamber sealingly secured to the first opening forsealing the first opening; the first opening communicating with aninterior volume of the holding chamber.